IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59113-6.html
   My bibliography  Save this article

Deep brain stimulation alleviates Parkinsonian motor deficits through desynchronizing GABA release in mice

Author

Listed:
  • Zongyi Xu

    (Fudan University)

  • Wei Duan

    (Fudan University)

  • Shuyu Yuan

    (Fudan University)

  • Xiaoxue Zhang

    (Fudan University)

  • Chong You

    (Fudan University)

  • Jin-Tai Yu

    (Fudan University)

  • Jian Wang

    (Fudan University)

  • Jia-Da Li

    (Central South University)

  • Suixin Deng

    (Central South University)

  • Yousheng Shu

    (Fudan University)

Abstract

High-frequency deep brain stimulation (DBS) at subthalamic nucleus (STN) is an effective therapy for Parkinson’s disease (PD), but the underlying mechanisms remain unclear. Here we find an important role of asynchronous release (AR) of GABA induced by high-frequency stimulation (HFS) in alleviating motor functions of dopamine-depleted male mice. Electrophysiological recordings reveal that 130-Hz HFS causes an initial inhibition followed by desynchronization of STN neurons, largely attributable to presynaptic GABA release. Low-frequency stimulation at 20 Hz, however, produces much weaker AR and negligible effects on neuronal firing. Further optogenetic and cell-ablation experiments demonstrate that activation of parvalbumin axons, but not non-parvalbumin axons, from external globus pallidus (GPe) is both necessary and sufficient for DBS effects. Reducing AR diminishes the high-frequency DBS effect, while increasing AR allows low-frequency DBS to achieve a therapeutic benefit. Therefore, asynchronous GABA release from GPe PV neurons may contribute significantly to the therapeutic effects of high-frequency DBS.

Suggested Citation

  • Zongyi Xu & Wei Duan & Shuyu Yuan & Xiaoxue Zhang & Chong You & Jin-Tai Yu & Jian Wang & Jia-Da Li & Suixin Deng & Yousheng Shu, 2025. "Deep brain stimulation alleviates Parkinsonian motor deficits through desynchronizing GABA release in mice," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59113-6
    DOI: 10.1038/s41467-025-59113-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59113-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59113-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59113-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.